More than 400 million people around the world suffer from crippling, chronic pain caused by joint diseases, osteoporosis, spine disorders and musculoskeletal trauma. Osteoarthritis, the most common type of arthritis, affects more than 21 million Americans and is a leading cause of disability in the United States. By the year 2020, an estimated 60 million people in the U.S. will have some form of arthritis. Besides the physical toll, arthritis costs the U.S. nearly $65 billion annually. Arthritis is second only to heart disease as a cause of work disability. See MMWR (1999) 48:349–353.
Arthritis usually causes stiffness, pain and fatigue. In some people, only a few joints are affected and the impact may be small. In other people, the entire body system may be affected.
Known therapies for arthritis and inflammatory conditions are usually palliative and based on the use of analgesic or anti-inflammatory agents and physical modalities. Because anti-inflammatories (e.g., NSAIDs) confer potentially high risk for serious NSAID-induced gastrointestinal side effects and renal toxicity, therapies are needed that will be analgesic, anti-inflammatory, safe and favorably modify the disease history.
The newer class of NSAIDs (e.g. Vioxx™, Celebrex™) are based on the selective inhibition of COX-2. While COX-2 inhibitors have minimized gastrointestinal complications, they still maintain contraindications for congestive heart failure and renal dysfunction. See Wilcox et al., Arch. Intern. Med. (1994) 15:42–45; Perneger et al., N Eng J Med (1994) 331:1675–1679; and Everts et al., Clin. Rheumatol (2000) 19:331–43.
Thus, there is a serious need for an effective treatment and method of prevention of arthritis and other rheumatic and skeletal conditions that do not cause serious side effects. The present invention provides compositions and methods for treatment and prevention of arthritis and related conditions, while avoiding many of the problems associated with current treatments. These compositions have the further benefit of increased efficacy and stability and a reduction of arachidonic acid and eicosanoid production in cells.